What’s New in Non-Small Cell Lung Cancer Research?

Prevention

Tobacco

Prevention offers the greatest opportunity to fight lung cancer. Although decades have passed since the link between smoking and lung cancers became clear, smoking is still responsible for most lung cancer deaths. Research is continuing on:

Ways to help people quit smoking and stay tobacco-free through counseling, nicotine replacement, and other medicines

Ways to convince young people to never start smoking

Inherited differences in genes that may make some people much more likely to get lung cancer if they smoke or are exposed to someone else’s smoke

Environmental causes

Researchers also continue to look into some of the other causes of lung cancer, such as exposure to radon and diesel exhaust. Finding new ways to limit these exposures could potentially save many more lives.

Diet, nutrition, and medicines

Researchers are looking for ways to use vitamins or medicines to prevent lung cancer in people at high risk, but so far none have been shown to clearly reduce risk.

Some studies have suggested that a diet high in fruits and vegetables may offer some protection, but more research is needed to confirm this. While any protective effect of fruits and vegetables on lung cancer risk is likely to be much smaller than the increased risk from smoking, following the American Cancer Society dietary recommendations (such as staying at a healthy weight and eating a diet high in fruits, vegetables, and whole grains) may still be helpful.

Early detection

As mentioned in Can Non-Small Cell Lung Cancer Be Found Early?, screening with spiral CT scans in people at high risk of lung cancer (due to smoking history) lowers the risk of death from lung cancer, when compared to chest x-rays.

Another approach now being studied uses newer, sensitive tests to look for cancer cells in sputum samples. Researchers have found several changes often seen in the DNA of lung cancer cells. Studies are looking at tests that can spot these DNA changes to see if they can find lung cancers at an earlier stage.

Diagnosis

Fluorescence bronchoscopy

Also known as autofluorescence bronchoscopy, this technique might help doctors find some lung cancers earlier, when they are likely to be easier to treat. For this test, the doctor inserts a bronchoscope through the mouth or nose and into the lungs. The end of the bronchoscope has a special fluorescent light on it, instead of a normal (white) light.

The fluorescent light causes abnormal areas in the airways to show up in a different color than healthy parts of the airway. Some of these areas might not be visible under white light, so the color difference can help doctors find these areas sooner. Some cancer centers now use this technique to look for early lung cancers, especially if there are no obvious tumors seen with normal bronchoscopy.

Virtual bronchoscopy

This imaging test uses a chest CT scan to create a detailed 3-dimensional picture of the airways in the lungs. The images can be viewed as if the doctor were actually using a bronchoscope.

Virtual bronchoscopy has some possible advantages over standard bronchoscopy. First, it is non-invasive and doesn’t require anesthesia. It also helps doctors view some airways that they might not able to get to with standard bronchoscopy, such as those being blocked by a tumor. But this test has some drawbacks as well. For example, it doesn’t show color changes in the airways that might indicate a problem. It also doesn’t let a doctor take samples of suspicious areas like bronchoscopy does. Still, it can be a useful tool in some situations, such as in people who might be too sick to get a standard bronchoscopy.

This test will probably become more available as the technology improves.

Electromagnetic navigation bronchoscopy

Lung tumors near the center of the chest can be biopsied during bronchoscopy, but bronchoscopes have trouble reaching the outer parts of the lungs, so tumors in these areas often need to be biopsied using a needle passed through the skin.

This newer approach can help a doctor use a bronchoscope to biopsy a tumor in the outer part of the lung. First, CT scans are used to create a virtual bronchoscopy. The abnormal area is identified, and a computer helps guide a bronchoscope to the area so that it can be biopsied. The bronchoscope used has some special attachments that allow it to reach further than a regular bronchoscope.

This takes special equipment and training, and it is not widely available at this time.

Treatment

Surgery

Doctors now use video-assisted thoracic surgery (VATS) to treat some small lung tumors. This procedure lets doctors remove parts of the lung through smaller incisions, which can result in shorter hospital stays and less pain for patients. Doctors are now studying if VATS can be used for larger lung tumors.

In a newer approach to this type of operation, the surgeon sits at a specially designed control panel inside the operating room to maneuver long surgical instruments using robotic arms. This approach, known as robotic-assisted surgery, is now being used in some larger cancer centers.

Real-time tumor imaging

Researchers are looking to use new imaging techniques, such as four-dimensional computed tomography (4DCT), to help improve treatment. In this technique, the CT machine scans the chest continuously for about 30 seconds. It shows where the tumor is in relation to other structures as a person breathes, as opposed to just giving a ‘snapshot’ of a point in time, like a standard CT does.

4DCT can be used to determine exactly where the tumor is during each part of the breathing cycle, which can help doctors deliver radiation to a tumor more precisely. This technique might also be used to help show if a tumor is attached to or invading important structures in the chest, which could help doctors determine if a patient might be eligible for surgery.

Radiation therapy

Several newer methods of giving radiation therapy have become available in recent years, For example, some newer radiation therapy machines have imaging scanners built into them. This advance, known as image guided radiation therapy (IGRT), lets the doctor take pictures of the lung and make minor adjustments in aiming just before giving the radiation. This may help deliver the radiation more precisely, which might result in fewer side effects.

Chemotherapy

New combinations: Many clinical trials are looking at newer combinations of chemotherapy drugs to determine which are the safest and most effective. This is especially important in patients who are older and have other health problems. Doctors are also studying better ways to combine chemotherapy with radiation therapy and other treatments.

Lab tests to help predict if chemo will be helpful: Doctors know that adjuvant chemotherapy after surgery may be more helpful for some people with early (stage I or II) cancers than for others, but figuring out which patients to give it to is not easy. In early studies, newer lab tests that look at patterns of certain genes in the cancer cells have shown promise in telling which people might benefit most. Larger studies of these tests are now trying to confirm their usefulness.

Other lab tests may help predict whether a lung cancer will respond to particular chemo drugs. For example, studies have found that tumors with high levels of the ERCC1 protein are less likely to respond to chemo that includes cisplatin or carboplatin, while tumors with high levels of the RRM1 protein seem less likely to respond to chemo with gemcitabine. Doctors are now looking to see if tests for these markers can help guide the choice of treatment, so these are not a part of standard treatment.

Targeted therapy drugs

Researchers are learning more about the inner workings of lung cancer cells that control their growth and spread. This is being used to develop new targeted therapy drugs. Many of these are already being used to treat NSCLC. Others are now being tested in clinical trials to see if they can help people with advanced lung cancer live longer or relieve their symptoms. Newer targeted drugs being studied include ganetespib, nintedanib, selumetinib, dacomitinib, and custirsen.

Researchers are also working on lab tests to help predict which patients might be helped by which drugs. Studies have found that some patients do not benefit from certain targeted therapies, whereas others are more likely to have their tumors shrink. For example, a test can find changes in the EGFR gene that make it much more likely that a person’s lung cancer will respond to treatment with a targeted drug called an EGFR inhibitor. Similar gene tests for other targeted treatments are now being studied. Predicting who might benefit could save some people from trying treatments that are unlikely to work for them and would probably cause unneeded side effects.

Maintenance therapy

For people with advanced lung cancers who get chemotherapy, combinations of 2 chemo drugs (sometimes along with a targeted drug) are typically given for about 4 to 6 cycles. Some studies have found that with cancers that have not progressed, continuing treatment beyond the 4 to 6 cycles with a single chemo drug such as pemetrexed or with a targeted drug may help some people live longer. This is known as maintenance therapy. A possible downside to this continued treatment is that people may not get a break from treatment side effects. Some doctors now recommend maintenance therapy, while others await further research on this topic.

Immune treatments

Researchers are developing immunotherapy drugs that can help the body’s immune system fight the cancer.

Immune checkpoint inhibitors: Cancer cells can sometimes avoid being attacked by the body’s immune system by using certain “checkpoints” that normally keep the immune system in check. For example, cancer cells often have a lot of a protein called PD-L1 on their surface that helps them evade the immune system. New drugs that block the PD-L1 protein, or the corresponding PD-1 protein on immune cells called T cells, can help the immune system recognize the cancer cells and attack them.

Nivolumab (Opdivo) and pembrolizumab (Keytruda) are anti-PD-1 drugs that have been shown to shrink or slow the growth of some tumors. Atezolizumab (Tecentriq) is an anti-PD-L1 drug that has also been shown to shrink some tumors. These drugs are now approved for use in advanced NSCLC. They are typically used after certain other treatments have been tried, although pembrolizumab can also be used as the first treatment in some cases.

Other, similar drugs such as MEDI4736 might also shrink some lung cancer tumors. Large studies of these new drugs are now being done.

Vaccines: Several types of vaccines for boosting the body’s immune response against lung cancer cells are being tested in clinical trials. Unlike vaccines against infections like measles or mumps, these vaccines are designed to help treat, not prevent, lung cancer. These types of treatments seem to have very limited side effects, so they might be useful in people who can’t tolerate other treatments.

Some vaccines are made up of parts of proteins commonly found on lung cancer cells. For example, the MUC1 protein is found on some lung cancer cells. A vaccine called TG4010 causes the immune system to react against the MUC1 protein. Early research has suggested this vaccine might be helpful when given along with chemo. More studies are planned to see if the vaccine will help patients live longer.

At this time, lung cancer vaccines are only available in clinical trials.

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